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Regional Comparison of the Neurogenic Effects of CNTF-Derived Peptides and Cerebrolysin in AβPP Transgenic Mice
- Source :
- Journal of Alzheimer's Disease. 27:743-752
- Publication Year :
- 2011
- Publisher :
- IOS Press, 2011.
-
Abstract
- Adult neurogenesis, the production of new neurons in certain brain regions, is known to decrease with age and the loss of neurogenic potential has been implicated in Alzheimer's disease (AD), a leading cause of dementia in the elderly. Cerebrolysin (CBL) has been shown to increase neurogenesis in models of stroke and AD. CBL is composed of small peptides with activity similar to neurotrophic factors including ciliary neurotrophic factor (CNTF), which may mediate its neurogenic effects. This study compares the effects of CBL and two peptides with corresponding to an active region of CNTF (Peptide 6 and 6A) across neurogenic brain regions in amyloid-β protein precursor (AβPP) transgenic (tg) mice. Both CBL and Peptides 6 and 6A were able to increase the numbers of neuroblasts (DCX+ cells) and BrdU+ cells in a regionally specific manner across the subventricular zone, olfactory bulb, and hippocampus. The increased generation of new cells and cell survival in animals treated with Peptides 6 and 6A was accompanied by an increase in PCNA+ cells. In contrast, AβPP tg mice treated with CBL displayed reduced levels of TUNEL staining, while levels of PCNA were unaltered. Collectively these results demonstrate that while CBL and Peptides 6 and 6A all potentiate neurogenesis in the AβPP tg mice, their relative modes of action may differ with CBL associated with reduced apoptosis and Peptides 6 and 6A working by augmenting cell proliferation. These results are consistent with a potential therapeutic relevance for Peptides 6 and 6A in AD and other disorders characterized by neurogenic deficits.
- Subjects :
- Doublecortin Domain Proteins
Doublecortin Protein
Neurogenesis
Subventricular zone
Neuropeptide
Mice, Transgenic
Ciliary neurotrophic factor
Article
Amyloid beta-Protein Precursor
Mice
chemistry.chemical_compound
Neuroblast
Alzheimer Disease
Neurotrophic factors
Proliferating Cell Nuclear Antigen
In Situ Nick-End Labeling
medicine
Animals
Humans
Ciliary Neurotrophic Factor
Amino Acids
Amyloid beta-Peptides
Cell Death
biology
General Neuroscience
Neuropeptides
Brain
General Medicine
Molecular biology
Peptide Fragments
Olfactory bulb
Cell biology
Mice, Inbred C57BL
Disease Models, Animal
Psychiatry and Mental health
Clinical Psychology
medicine.anatomical_structure
Bromodeoxyuridine
Gene Expression Regulation
chemistry
Cerebrolysin
Mutation
biology.protein
Geriatrics and Gerontology
Peptides
Microtubule-Associated Proteins
Subjects
Details
- ISSN :
- 18758908 and 13872877
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease
- Accession number :
- edsair.doi.dedup.....9fbed28bea7076fe4b04ae76580104d8